This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Plasmodium falciparum causes the most severe form of human malaria and is responsible for approximately two million deaths per year (Snow et al., 2005). Deaths are due mainly to a complication known as cerebral malaria, in which infected red blood cells (RBCs) adhere to the walls of blood vessels in the brain. The proteins that enable RBCs to adhere to blood vessels are synthesized by the parasite and transported to the RBC surface. This is an impressive feat given that the RBC is devoid of trafficking machinery. To accomplish this, the parasite generates novel structures within the host cell cytoplasm to mediate protein transport. These include compartments called the Maurer[unreadable]s clefts (MC), which play an important role in the trafficking of parasite proteins to the surface of the host cell. About one third of the way through its 48 hour intraerythrocytic cycle, parasite-derived virulence proteins are inserted into the RBC membrane. These proteins can mediate adhesion to the vascular endothelium, resulting in the accumulation of infected RBCs in organs such as the brain and placenta, which can be lethal (Kyes et al., 1999). These proteins can also bind and inhibit maturation of dendritic cells and may modulate the immune response (Urban et al., 1999). It is a major aim of this project to increase our understanding of the organization, morphology and function of structures known as the Maurer[unreadable]s clefts. These organelles are formed de novo by the parasite in its host cell[unreadable]s cytoplasm and are thought to be involved in the delivery of proteins to the surface of the infected RBC. A better knowledge of the MC and of the transport of different components to and from the MC could lead to the development of new antimalarial strategies that interrupt the trafficking and delivery of virulence factors. This could prevent adhesion of the infected RBCs to the vascular endothelium or uninfected red blood cells.